Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Transdisciplinary Canadian team to build global AMR network
York University this week announced a $2 million grant from the Canadian Institutes of Health Research to support the development of a global network to address infectious disease and antimicrobial resistance.
The One Health Network for the Global Governance of Infectious Diseases and Antimicrobial Resistance (GRIDD) will be co-led by York University and the University of Ottawa and will include a transdisciplinary team of researchers from the social sciences and the human, animal, and environmental health sciences. The network will be closely integrated with related European efforts.
"As the causes of antimicrobial resistance are complex, our strategies to address it need to foster intersectoral policy coordination on a global scale to improve stewardship of this precious resource," Mary Wiktorowiz, PhD, a professor of global health policy and governance at York University, said in a university press release.
Feb 18 York University press release
NIH to fund new treatment strategy for resistant lung infections
Scientists from Purdue University will receive $3.2 million from the National Institutes of Health to develop a new treatment for antibiotic-resistant lower respiratory infections.
The money will enable the scientists to continue development of new inhalation therapies that incorporate synergistic antibiotics into a nano-sized liposome. Using liposomes for inhalation therapy minimizes local irritation in the airways, which can compromise patients' compliance, and allows for controlled release of the drugs.
"Our research not only develops new inhalation therapies, but also examines the mechanism of drug-induced pulmonary side effects and tries to find out how liposomes protect the airways from such side effects," lead researcher Qi Zhou, PhD, an assistant professor in Purdue's College of Pharmacy, said in a university press release. "In addition, such platform may also be applied for the treatment of other lung infections including tuberculosis and viral lung infections by loading different drugs."
Researchers from the University of Michigan, University of North Carolina, and Monash University in Australia are also involved in the project.
Feb 20 Purdue University press release
Surveys find less antibiotic-resistant bacteria in UK chicken meat
Originally published by CIDRAP News Feb 20
The United Kingdom's Food Standards Agency (FSA) released two surveillance reports this week on antimicrobial resistance (AMR) in chicken meat.
The two surveys looked at antibiotic-resistant Escherichia coli and Campylobacter in fresh chicken sold at UK retail stores in 2017 and 2018. Of the 309 samples tested for resistant E coli, no samples were positive for carbapenem resistance or plasmid-mediated colistin resistance, while 23 (8.4%) expressed extended-spectrum beta-lactamase (ESBL)-phenotype resistance, 16 (5.2%) expressed AmpC-phenotype resistance, and 3 expressed both ESBL- and AmpC-phenotype resistance.
Overall, the proportion of chicken meat samples positive for ESBL-producing E coli fell from 65.4% in 2013-2014 to 8.4% in 2018, and AmpC-producing E coli fell from 16.3% in 2016 to 5.2% in 2018. The FSA said this decrease could be linked to the banning of cephalosporins in poultry meat flocks by the UK Poultry Council in 2012.
Of the 392 samples tested for resistant Campylobacter bacteria, ciprofloxacin resistance was detected in 52% of Campylobacter jejuni isolates (171/328), and 48% of Campylobacter coli isolates (31/65). Multidrug resistance was found in 5 of 328 C jejuni isolates (2%) and 6 of 65 C coli isolates (9%). Overall, the proportions of antibiotic-resistant and multidrug-resistant Campylobacter isolates identified were similar to those found in previous survey years.
"While there is evidence that AMR bacteria are present on chicken sold in the UK, it is encouraging to see the levels holding steady and even reducing," Paul Cook, FSA science lead in microbiological risk assessment, said in an agency press release. "The risk of getting AMR-related infections through eating or preparing contaminated meat remains very low as long as you follow good hygiene and cooking practices."
Feb 18 FSA press release
Feb 18 FSA E coli survey
Feb 18 FSA Campylobacter survey
Study: Contact isolation doesn't reduce spread of resistant organisms
Originally published by CIDRAP News Feb 20
A study of patients in four European hospitals has found that contact isolation showed no benefit when added to standard precautions for controlling the spread of ESBL-producing Enterobacteriaceae (ESBL-E) on non-critical care wards with extensive surveillance screening, researchers reported yesterday in the Lancet Infectious Diseases.
In the cluster-randomized trial conducted at university hospitals in Germany, the Netherlands, Spain, and Switzerland, patients in medical, surgical, and combined medical-surgical wards were randomized to continue standard precautions alone or implement contact isolation alongside standard precautions for 12 months, followed by a 1-month washout period and 12 months of an alternative strategy. Patients were screened for ESBL-E on carriage within 3 days of admission, once a week thereafter, and on discharge. The primary outcome was the incidence density of ESBL-E.
Between Jan 6, 2014, and Aug 31, 2016, 38,357 patients were admitted to the hospital wards. Among 15,184 patients with a length of stay of more than 1 week, 11,368 patients (75%) were screened at least twice. The incidence density of ward-acquired ESBL-E was 6.0 events per 1,000 patient-days at risk (95% confidence interval [CI], 5.4 to 6.7) during periods of contact isolation and 6.1 (95% CI, 5.5 to 6.7) during periods of standard precautions (P = 0·9710). Multivariable analysis adjusted for length of stay, percentage of patients screened, and prevalence in first screening cultures yielded an incidence rate ratio of 0.99 (95% CI, 0.80 to 1.22; P = 0.9177) for care under contact isolation compared with standard precautions.
"The results of this trial suggest that current real-life practice in many countries, including the targeted identification of carriers and expanded use of contact isolation, is ineffective in preventing the spread of ESBL-E in endemic settings," the authors conclude.
The findings are significant because while many guidelines recommend the use of contact isolation for patients colonized or infected with multidrug-resistant bacteria, several studies in recent years have questioned their effectiveness. In addition, research has shown that patients under contact isolation express greater dissatisfaction with their treatment.
Feb 19 Lancet Infect Dis abstract
Two tests detect carbapenem resistance in lower respiratory tract samples
Originally published by CIDRAP News Feb 20
Spanish investigators yesterday in the Journal of Antimicrobial Chemotherapy reported good results from using two commercial rapid diagnostic tests—Xpert Carba-R and Eazyplex SuperBug CRE—to detect bacterial carbapenem resistance genes directly in lower respiratory tract samples.
The researcher team used the two tests—the former a real-time polymerase chain reaction (PCR) test and the other employing loop-mediated isothermal amplification—for detecting carbapenemase carriage in Enterobacteriaceae directly from bronchoalveolar lavage (BAL). The researchers added well-characterized carbapenemase-producing Enterobacteriaceae strains to the BAL samples to observe how the tests would perform.
Xpert Carba-R demonstrated 100% agreement with carbapenemase characterization by PCR and sequencing for all final bacteria concentrations. Eazyplex SuperBug CRE showed 100%, 80% and 27% agreement with PCR and sequencing at diminishing pathogen concentrations. False-negative results for Eazyplex SuperBug CRE matched the highest cycle threshold values for Xpert Carba-R. Hands-on time for both assays was about 15 min, but Eazyplex SuperBug CRE results were available within 30 min, whereas Xpert Carba-R took around 50 min.
The authors say their results could be used as proof-of-concept data for validating the tests for this purpose.
Feb 19 J Antimicrob Chemother abstract
CARB-X funs antibacterial peptide development
Originally published by CIDRAP News Feb 18
CARB-X said today it has awarded Lytica Therapeutics, of Cambridge, Massachusetts, up to $5.3 million to develop antibacterial peptides that have broad activity against multidrug-resistant bacteria for treating lung and other infections.
In a news release, CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) said Lytica could receive up to $11.6 million in additional funding if the project achieves certain development milestones, for a potential total of $16.9 million.
"There is an urgent need for innovative therapeutics and approaches to drug-resistant infections that, today, are killing some 700,000 people around the world each year," said Erin Duffy, PhD, chief of research and development at CARB-X. "The Lytica project is in the early phases of development, but if successful and ultimately approved for use in patients, it could represent tremendous improvement in the treatment of multidrug-resistant gram-negative pathogens."
Antimicrobial peptides are a family of peptides with therapeutic potential, but their clinical use is limited mostly to topical applications because of problems with toxicity, stability, and efficacy. Lytica's proprietary "stapling" technology aims to overcome these hurdles.
The company has produced compounds called stapled antimicrobial peptides that have demonstrated potent activity against multidrug-resistant bacteria, stability against degrading, and wide therapeutic potential. If successful, the project could produce treatments for a wide range of serious infections, including lung, urinary tract, and intra-abdominal infections.
Since its launch in 2016, CARB-X, a public-private partnership, has announced 57 awards exceeding $193 million, with additional funds possible if project milestones are met. Its goal is to invest $500 million by the end of 2021.
Feb 18 CARB-X news release
UK report examines airborne antimicrobial resistance
Originally published by CIDRAP News Feb 18
In a report today on airborne antimicrobial resistance, the UK Environment Agency says much more research is needed to determine how much of a health risk it poses.
The review and analysis of 88 relevant papers obtained from three academic databases found that, despite differences in study environments, methods used, and antibiotics studied, some basic conclusions emerged. Among those conclusions are that tetracycline resistance appears to be more prevalent in agriculturally associated air, industrial activities involving fecal matter (including farms) are associated with the highest levels of multidrug resistance reported to date, and the ubiquitous use of azole antifungals in medicine and agriculture—along with the ability of fungi to travel long distances in the air—makes airborne antifungal resistance a relevant threat.
Some of the questions that still need to be addressed, according to the report, are whether air is a primary route of antimicrobial resistance transmission to humans and other vulnerable hosts, and how the resulting risk compares with other transmission methods. The researchers say exploring the biophysics of airborne antimicrobial resistance could help answer some of these questions.
"More research is recommended to close knowledge gaps and test emergent hypotheses," the authors of the report write. "Also needed is a more concerted effort to report and share the results of antimicrobial susceptibility testing in a standardised way, and more careful and standardised collection and reporting of air sampling."
Feb 18 UK Environment Agency report
Study: In PCV-13 era, new strains of resistant pneumococci emerging
Originally published by CIDRAP News Feb 18
An analysis of Streptococcus pneumoniae isolates collected from young children in primary care settings has found reduced susceptibility to several antibiotic classes in the 13-valent pneumococcal conjugate vaccine (PCV-13) era, researchers report today in Clinical Infectious Diseases.
In the prospective cohort study, investigators from Rochester General Hospital Research Institute in Rochester, New York, collected nasopharyngeal and middle ear fluid samples from children ages 6 to 36 months during acute otitis media (ear infection) and routine healthy visits at primary care pediatric practices in Rochester from 2006 through 2016. They then performed antibiotic susceptibility testing on S pneumoniae isolates against a panel of 16 antibiotics from 10 classes. All children were up to date on vaccines, receiving the PCV-7 vaccine from 2006 until April 2010 and PCV-13 after April 2010.
From 2006 through 2016, 1,201 S pneumoniae isolates were characterized from 1,072 visits of 448 children. Analysis of susceptibility trends showed that, after introduction of PCV-13, susceptibility to S pneumoniae to antibiotics, especially penicillin, initially improved, largely because of the disappearance of serotype 19A, which is included in PCV-13. But beginning in 2013, antibiotic susceptibility among S pneumoniae strains began decreasing with the emergence of three serotypes (11A, 35B, and 35F) not included in PCV-13. In addition to reduced susceptibility to penicillin, the most recent isolates also showed reduced susceptibility to third-generation cephalosporins, fluoroquinolones, and carbapenems.
The authors of the study say the reduced susceptibility to third-generation cephalosporins, fluoroquinolones, and carbapenems could have implications for future treatment of invasive pneumococcal disease. They also note that neither of the two PCVs in advanced development (PCV-15 and PCV-20) includes serotypes 35B or 35F.
Feb 18 Clin Infect Dis abstract
Canadian hospitals see significant decrease in antibiotic use
Originally published by CIDRAP News Feb 17
A major reduction in the use of fluoroquinolones has driven a 12% decrease in total antibiotic use in Canadian hospitals in recent years, according to a new study in Antimicrobial Resistance and Infection Control.
In the retrospective surveillance study, acute care hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual data on all systemic antimicrobial use (AMU) from 2009 to 2016. National and regional rates of AMU were calculated and analyzed using defined daily doses per 1,000 patient-days (DDD/1,000 pd), and AMU data were used to rank the top antimicrobial agents used individually, by class/subclass, and by year. Overall, 16 to 18 CNISP adult hospitals per year provided data, with representation from 6 sites in western Canada, 15 in central Canada, and 1 in eastern Canada.
From 2009 to 2016, the data showed a 12% reduction in total AMU (from 654 to 573 DDD/1,000 pd, P = 0.03). Fluoroquinolones accounted for most of this decrease, with a 47% reduction in combined oral and intravenous use, (from 129 to 68 DDD/1,000 pd, P < 0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1,000 pd), piperacillin-tazobactam (53 DDD/1,000 pd), ceftriaxone (49 DDD/1,000 pd), vancomycin (combined oral and intravenous use: 44 DDD/1,000 pd), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1,000 pd).
Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016, by 46% (P = 0.002) and 26% (P = 0.002) respectively. Use of ceftriaxone (85% increase, P = 0.0008) and oral amoxicillin-clavulanate (140% increase, P < 0.0001) increased significantly but contributed only a small component (8.6% and 5.0%, respectively) of overall use.
The authors of the study say it's unclear whether the reduction in fluoroquinolone use is related to stewardship efforts, warnings of adverse effects associated with fluoroquinolone use in the United States and Canada, or a combination.
Feb 13 Antimicrob Resist Infect Control study
Electronic alerts linked to fewer C diff tests, lower rates, review finds
Originally published by CIDRAP News Feb 17
A systematic review of 11 studies indicates that the use of electronic alerts for diagnostic stewardship for Clostridioides difficile infection (CDI) was associated with reductions in CDI testing, inappropriate CDI testing, and rates of CDI, researchers reported in Clinical Infectious Diseases.
The aim of the study was to determine whether CDI testing-oriented electronic alerts, which aim to discourage inappropriate testing and subsequent unnecessary antibiotic treatment, have an effect not just on process indicators, such as laboratory ordering, but also on intermediate outcomes (rates of CDI testing and inappropriate testing) and patient-centered outcomes (rates of CDI). To answer those questions, the researchers searched six databases for studies evaluating the association between the alerts and CDI testing volume and/or CDI rate.
The 11 studies that met the criteria for inclusion varied significantly in alert triggers and study outcomes. Nine studies used an alert discouraging CDI testing when the patient had recent laxative use, 7 used an alert discouraging CDI testing with lack of clinical indication for testing, and 6 used an alert discouraging CDI testing when the patient had recent CDI testing; 11 articles studied the number of tests ordered, 6 studied the number of appropriate tests, and 7 studied the CDI rate.
Six of the 11 studies demonstrated a statistically significant decrease in CDI testing volume, 6 of 6 studies evaluating appropriateness of CDI testing found a significant reduction in the proportion of inappropriate testing, and 4 of 7 studies measuring CDI rate demonstrated a significant decrease in the CDI rate in the post- vs pre-intervention periods. The magnitude of the increase in appropriate CDI testing varied, with some studies reporting an increase with minimal clinical significance.
The authors of the review note that, while alert-based interventions appeared to be largely successful in achieving the desired changes, most studies included multiple co-interventions, and none were randomized. In addition, they point out that unintended adverse consequences, such as underdiagnosis or delayed diagnosis of CDI, and alert fatigue—in which physicians have trouble distinguishing between clinically meaningful and non-meaningful alerts—remain understudied.
Feb 15 Clin Infect Dis abstract
